[unreadable] Colorectal cancer is the second leading cause of cancer mortality in the United States, with an estimated 56,700 deaths in 2001. Most colorectal adenocarcinomas arise from benign, neoplastic adenomatous polyps. Because colorectal cancer has an identifiable precursor lesion (adenomatous polyps), a unique opportunity for early detection and intervention exists if modifiable risk factors for polyps can be identified. Variations in incidence of colorectal cancer with respect to geography and migration suggest an important environmental component to colorectal cancer risk. Selenium, an essential trace element found in cereals, wheat, dairy products, meat and fish, may prevent carcinogenesis through a number of biochemical pathways. One way that selenium might reduce cancer risk is by increasing apoptosis, or programmed cell death. This process provides a mechanism to remove damaged cells, which decreases the chance that abnormal cells will proliferate and develop into malignancies. Clinical trial data suggest a strong protective effect of selenium on cancer incidence; however, results from observational studies are inconclusive. Many of the case-control studies of selenium and colon cancer did not exclude participants with advanced disease, making it difficult to draw a conclusion given the impact that advanced disease and cancer treatment have on selenium levels in the body. Very few studies have addressed the association between selenium and colorectal adenomas and all studies that have were very small. Finally, no epidemiologic studies have assessed the potential biological pathway through apoptosis. The proposed study will make use of existing biological samples from two large studies to investigate the relation between serum selenium and early stage colorectal adenocarcinoma, in addition to its precursor lesion (adenomatous polyps). Most notably, we propose to investigate the biologic mechanism of apoptosis, which has not been previously evaluated in a human population. This research is of public health importance because selenium is a potential chemopreventive agent for colorectal cancer. [unreadable] [unreadable]